| Name: | Description: | Size: | Format: | |
|---|---|---|---|---|
| 2.14 MB | Adobe PDF |
Authors
Advisor(s)
Abstract(s)
A anemia falciforme é a doença hematológica genética mais comum, sendo diagnosticada em aproximadamente 305.000 nascimentos por ano e com milhões de pessoas afetadas em todo o mundo. É um importante contributo para a mortalidade de menores de 5 anos nos países de baixa renda. Nesse estudo pretendemos analisar a associação de cinco SNPs com 21 aspectos clínicos e hematologicos da SCD e a resposta á HU, em população de crianças angolana. Para isso, selecionamos SNPs, encontrados em genes em trans (rs11759328 (ARHGAP), rs333 (CCR5), rs10793902 (ASS1), rs9483947 (MAP3K5) e rs836729 (Tox)) e estão relacionados com a gravidade da doença, aos níveis de HbF, a resposta a HU e na modulação da expressão de genes da globina. Na associação entre os genótipos e os fenótipos para o SNP rs10793902 (ASS1) encontramos ligeiro aumento da bilirrubina indireta e uma diminuição dos episódios de AVCs, e para o SNP rs9483947 (MAP3K5) um aumento significativo de LDH. Nossos achados não demonstraram associação do SNPs com a resposta à HU. Sendo essas associações relelevantes para o prognóstico da doença, consideramos que essa descoberta possa abrir caminho para futuras investigações, principalmente em outros biomarcadores que regulam a expressão dos genes onde encontram-se esses SNPs. Para verificar a associação dos SNPs e a resposta a HU, consideramos importante o aumento da população tratada, o período entre a administração do fármaco e a colheita da amostra. Com base nesses novos achados e sua importância, podemos buscar de novos biomarcadores que beneficiem milhares de pacientes afetados pela SCD.
ABSTRACT - Sickle cell anemia is the most common genetic hematologic disease, being diagnosed in approximately 305,000 births per year and with millions of people affected worldwide. It is an important contributor to under-5 mortality in low-income countries. In this study, we intend to analyze the association of five SNPs with 21 clinical and hematological aspects of SCD and the response to HU, in a population of Angolan children. For this, we selected SNPs, found in transgenes (rs11759328 (ARHGAP), rs333 (CCR5), rs10793902 (ASS1), rs9483947 (MAP3K5), and rs836729 (Tox)) and are related to disease severity, to HbF levels, the response to HU and in the modulation of the expression of globin genes. In the association between genotypes and phenotypes for SNP rs10793902 (ASS1) we found a slight increase in indirect bilirubin and a decrease in stroke episodes and for SNP rs9483947 (MAP3K5) a significant increase in LDH. Our findings showed no association of SNPs with the response to HU. As these associations are relevant for the prognosis of the disease, we believe that this discovery may open the way for future investigations, especially in other biomarkers that regulate the expression of genes where these SNPs are found. To verify the association of SNPs and the response to HU, we consider important the increase in the population treated, the period between drug administration, and sample collection. Based on these new findings and their importance, we can look for new biomarkers that benefit thousands of patients affected by SCD.
ABSTRACT - Sickle cell anemia is the most common genetic hematologic disease, being diagnosed in approximately 305,000 births per year and with millions of people affected worldwide. It is an important contributor to under-5 mortality in low-income countries. In this study, we intend to analyze the association of five SNPs with 21 clinical and hematological aspects of SCD and the response to HU, in a population of Angolan children. For this, we selected SNPs, found in transgenes (rs11759328 (ARHGAP), rs333 (CCR5), rs10793902 (ASS1), rs9483947 (MAP3K5), and rs836729 (Tox)) and are related to disease severity, to HbF levels, the response to HU and in the modulation of the expression of globin genes. In the association between genotypes and phenotypes for SNP rs10793902 (ASS1) we found a slight increase in indirect bilirubin and a decrease in stroke episodes and for SNP rs9483947 (MAP3K5) a significant increase in LDH. Our findings showed no association of SNPs with the response to HU. As these associations are relevant for the prognosis of the disease, we believe that this discovery may open the way for future investigations, especially in other biomarkers that regulate the expression of genes where these SNPs are found. To verify the association of SNPs and the response to HU, we consider important the increase in the population treated, the period between drug administration, and sample collection. Based on these new findings and their importance, we can look for new biomarkers that benefit thousands of patients affected by SCD.
Description
Mestrado em Tecnologias Moleculares em Saúde
Keywords
Anemia falciforme Hemoglobinopatias Genotipagem PCR SNPs Sickle cell anemia Hemoglobinopathies Genotyping Criança Children
Citation
Ramos AP. Variabilidade genética, expressão da hemoglobina fetal e severidade da doença em crianças com anemia das células falciformes [dissertation]. Lisboa: Escola Superior de Tecnologia da Saúde de Lisboa/Instituto Politécnico de Lisboa; 2021.
Publisher
Instituto Politécnico de Lisboa, Escola Superior de Tecnologia da Saúde de Lisboa